This proposal represens a continuation and extension of studies on the effects of central nervous system lesions on monoamines and other pharmacologically active substances and their biosynthetic enzymes in the brain. The major objective is to provide information regarding the specific neuronal elements whose integrity is necessary for the maintenance of the monoamines and the enzymes involved in their byosynthesis in the various anatomic subdivisions of brain. Since the effects of CNS lesions have been demonstrated to occur, at least in part, trans-synaptically, the research will include an investigation of the mechanisms by which degeneration of neurons in one area of brain influences monoamine biosynthesis in anatomic sites one or more synapses removed from the neurons destroyed. The availability of animals with specifc, anatomically defined neurochemical defects represents an excellent experimental tool for investigating the role of the biogenic amines in brain metabolism and behavior. We will, in addition, study the effect of lesions and nerve stimulation on the level of enzymes in the pineal which are under the control of environmental lighting as a model system for determining the neutral and molecular events underlying the regulation of enzyme synthesis by the nervous system.